Beta-Catenin and Development of the Urogenital System

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Abstract

The urogenital system is composed of the kidneys, gonads, urinary and reproductive tracts. Components of the urogenital system play many important roles in the body; kidneys function by regulating the body's fluid volume, acidity and mineral composition, while the reproductive tract is necessary for propagation of our species. Therefore, the study of urogenital system development is important in the understanding of disorders associated with both the kidneys and the reproductive tract and their treatment.
Urogenital system development begins with the formation of an epithelial tube, called the Wolffian duct. From the Wolffian duct forms a ureteric bud, which, along with the metanephric mesenchyme, will undergo a series of morphogenetic changes, eventually giving rise to the adult kidney. The Wolffian or M񬬥rian ducts, along with the bipotential gonads, will develop into the male or female reproductive tracts,respectively. Although many signals are involved in development of the urogenital system, canonical Wnt/beta-catenin signaling is known to play a significant role.
To better understand the role Wnt signaling plays in reproductive tract development, we conditionally removed beta-catenin from the Wolffian duct using a HoxB7cre line of mice. We determined that beta-catenin is necessary for M񬬥rian duct formation. Additionally, removal of beta-catenin from the Wolffian duct leads to premature differentiation, preventing degradation of the Wolffian duct in females and inhibiting proper formation of the Wolffian duct into components of the male reproductive tract. In addition to our mouse model, we validated the efficacy of small molecule inhibitors of Wnt signaling in embryonic kidney culture. Functional small molecule Wnt inhibitors will provide an important tool for the continued study of urogenital system development along with the potential treatment of diseases associated defective Wnt signaling.